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Aramwit P Yu BG Lavasanifar A Samuel J Kwon GS 《Journal of pharmaceutical sciences》2000,89(12):1589-1593
Studies have shown that the dose-limiting toxicity of amphotericin B (AmB), a key drug for systemic mycoses, depends on its self-aggregation state. In a step toward understanding the various factors in blood mediating the toxicity of AmB, we have investigated the effect of serum albumin, the most abundant plasma protein, on the aggregation state of AmB using absorption spectroscopy. The critical aggregation concentration (CAC) of AmB, which coincides with its concentration at the onset of toxicity (hemolysis), was 1.1 microM, but rose in proportion to the level of serum albumin (1.0 to 4.0% w/v). The CAC of AmB was 8.0 microM at 4.0% w/v serum albumin, which is considerably higher than peak therapeutic levels of AmB in plasma (i.e., 2.0 microM). Serum albumin (4.0% w/v) lowered the degree of aggregation of AmB (size of aggregates) above the CAC and increased its solubility. The results suggest that serum albumin attenuates the toxicity of AmB at a membrane level by affecting its aggregation state. In this way, serum albumin in blood may balance deleterious effects of AmB mediated by serum low-density lipoproteins. 相似文献
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P. Aramwit PharmD PhD O. Supasyndh MD T. Sriboonruang MSc 《Journal of clinical pharmacy and therapeutics》2008,33(6):685-690
Background: End‐stage renal disease (ESRD) is associated with marked alterations in the pharmacokinetics of many drugs, not only from reduction in renal clearance but also from changes in metabolic activity, bioavailability, volume of distribution and plasma protein binding. Objective: To study the pharmacokinetics of a single 8‐mg oral dose of rosiglitazone in patients with ESRD and requiring long‐term chronic ambulatory peritoneal dialysis (CAPD). Method: The medication was administered just before the first exchange of peritoneal dialysis fluid on the day that blood and peritoneal dialysate collection was performed. Results: In our CAPD patients the mean (±SD) Tmax and T1/2 of rosiglitazone were 1·20 ± 0·26 and 21·38 ± 21·96 h respectively. These values were different to those reported for healthy volunteers reported in previous studies. The mean area under the concentration–time curve (AUC(0–∞)) and an average maximum observed plasma concentration (Cmax) of rosiglitazone in our CAPD patients were 4203·56 ± 2916·97 ng h/mL and 409·67 ± 148·89 ng/mL respectively. These appear no different from those reported in healthy volunteers . Conclusion: The apparently significant difference in T1/2 of rosiglitazone in CAPD patients compared with healthy volunteers suggest that dose adjustment may be necessary in order to avoid toxicity. 相似文献
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Aramwit P Kerdcharoen T Qi H 《PDA journal of pharmaceutical science and technology / PDA》2006,60(4):211-217
Lyophilized nanosuspension formulation intended for intravenous administration has been developed. The in-vitro plasma compatibility of the formulation was evaluated under conditions that mimic intravenous injection. After reconstitution of the lyophilized nanosuspension formulation with sterile water for injection, the drug was then further diluted with 0.9 % w/v NaCl or 5% w/v dextrose to make concentrations of 1.5 and 5.0 mg/mL with each diluent. The 1.5-mg/mL solutions were diluted with plasma in the ratio of 1:1 and 1:2, and the 5.0-mg/mL solutions were diluted with plasma in the ratio of 1:2 and 1:10, to simulate different intravenous infusion rates. Different contributing factors for particle aggregation upon mixing with plasma-such as the concentration of active ingredient, the types of diluents, the formulation/plasma ratio dependent upon infusion rate and the plasma flow rate, and the incubation time-were evaluated with respect to particle aggregation. It was found that aggregation occurred very rapidly in all conditions and that more aggregation takes place with higher drug concentrations in the mixture with plasma. It was also found that there was minimum aggregation at the concentration of 1.5 mg/mL when delivered at an infusion rate of 2.5 mL/min. This combination is recommended for further toxicological and clinical evaluation. 相似文献
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Baralee Punyawudho Chankit Puttilerpong Suntchai Wirotsaengthong Pornanong Aramwit 《African journal of traditional, complementary, and alternative medicines》2013,10(2):310-315
Erectile dysfunction (ED) is one of the major health concerns affects the quality of life among Thai male. The treatment of ED by the first-line drugs is limited to a certain group of patients due to their side effects and costs. Alternative medicine can be beneficial for the treatment of ED. This is a randomized, double-blind, placebo-controlled, crossover study aimed to assess the efficacy and safety of Cappra®, a traditional herbal medicine which was used in Thailand for decades, for the treatment of mild and mild to moderate ED in Thai patients. A total of 63 patients with mild or mild to moderate ED were randomized to receive Cappra® or placebo for two weeks in the first period, followed by one week washout period. The patients were switched to the alternative treatment in the second period. The efficacy was assessed by the International Index of Erectile Function (IIEF) questionnaire and adverse events. Sixty one patients completed the study. There was an improvement of IIEF score for all domains in Cappra® group compared with placebo group. The mean change of IIEF score from baseline for erectile function domain of Cappra® was significantly higher than placebo (4.87 vs 3.44, p = 0.032). The most common adverse events were dizziness (13.3% Cappra®, 9.6% placebo), face numbness (1.6% Cappra®, 0% placebo), and tachycardia (1.6% Cappra®, 0% placebo). The results from this study demonstrated that Cappra® is effective and well-tolerated and can be used as alternative therapy for mild and mild to moderate ED. 相似文献
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